This project was undertaken to delineate the roles of phenotypically distinct T cell subpopulations in mediating tissue allograft rejection. We demonstrated that Lyt2+ T cells could reject class I but not class II disparate grafts and that L3T4+ T cells could reject class II but not class I disparate grafts. We subsequently investigated the ability of these distinct populations to reject skin grafts bearing (1), multiple minor-H disparities, and (2), a single minor-H disparity, the male specific H-Y antigen. Whereas both untreated and L3T4+ T cell populations can reject grafts bearing multiple minor-H disparities, it is not yet clear if the Lyt2+ population can do so in isolation. In the case of the rejection of H-Y disparate grafts, it is clear that neither purified population in isolation was able to effect the rejection of these grafts and that collaboration between T cell subpopulations was essential for rejection. Additional studies have investigated the ability to effect rejection of grafts by the addition of "carrier" determinants of varying disparities. For example, in a preliminary assay, the swift rejection of bm6 grafts (ordinarily poorly rejected by B6 mice) is accomplished by the addition of a class II disparity (bm12 x bm6) but not by a class I disparity (bml x bm6), suggesting that there may be a difference in the ability of helper cells of differing phenotypes to collaborate in effecting the rejection of allografts. By performing these assays using the adoptive transfer model, we hope to delineate the phenotypes of the cells required for such collaborative interactions.